Effects of dopamine depletion on LFP oscillations in striatum are task- and learning-dependent and selectively reversed by L-DOPA.

ABSTRACT

A major physiologic sign in Parkinson disease is the occurrence of abnormal oscillations in cortico-basal ganglia circuits, which can be normalized by L-DOPA therapy. Under normal circumstances, oscillatory activity in these circuits is modulated as behaviors are learned and performed, but how dopamine depletion affects such modulation is not yet known. We here induced unilateral dopamine depletion in the sensorimotor striatum of rats and then recorded local field potential (LFP) activity in the dopamine-depleted region and its contralateral correspondent as we trained the rats on a conditional T-maze task. Unexpectedly, the dopamine depletion had little effect on oscillations recorded in the pretask baseline period. Instead, the depletion amplified oscillations across delta (~3 Hz), theta (~8 Hz), beta (~13 Hz), and low-gamma (~48 Hz) ranges selectively during task performance times when each frequency band was most strongly modulated, and only after extensive training had occurred. High-gamma activity (65-100 Hz), in contrast, was weakened independent of task time or learning stage. The depletion also increased spike-field coupling of fast-spiking interneurons to low-gamma oscillations. L-DOPA therapy normalized all of these effects except those at low gamma. Our findings suggest that the task-related and learning-related dynamics of LFP oscillations are the primary targets of dopamine depletion, resulting in overexpression of behaviorally relevant oscillations. L-DOPA normalizes these dynamics except at low-gamma, linked by spike-field coupling to fast-spiking interneurons, now known to undergo structural changes after dopamine depletion and to lack normalization of spike activity following l-DOPA therapy.